Dr Thorsten Hagemann

MD PhD

Centre: Cancer and Inflammation

Fellowships:

MRC Clinician Scientist

Job Title: Clinical Senior Lecturer

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QMUL Directory

Research Interests

Dr Thorsten Hagemann's main research themes are in: Cancer Immunology, Metastasis and Invasion, Ovarian Cancer, Pancreatic Cancer and Tumour Angiogenesis

Blood-forming stem cells follow one of two different development pathways and differentiate into either lymphoid (T or B cells) or myeloid (all other white blood cells) cells. My research group is focused on understanding the molecular and cellular basis for the functional heterogeneity of the myeloid cell lineage. We employ molecular biology approaches to understand how innate immunity may contribute to human health and disease, particularly cancer.

We investigate the hypothesis that targeting specific signalling pathways in macrophages can alter immunity. This will provide fundamental information on the role of these signalling pathways in innate immunity, immune tolerance and innate immune function in cancer, chronic disease, transplantation or ageing.

These mechanisms may be deregulated and could represent potential therapeutic targets to modify innate immune responses in cancer. The molecules and mechanisms identified by those studies are then examined for human counterparts that may teach us about pathogenesis, and provide new tools for application in clinical trials that we undertake.

Although each researcher in the laboratory pursues a clearly defined project, great emphasis is placed on the synergies that can be realised through small teams of researchers working together on the following areas.

1. Regulation of myeloid cell differentiation and polarisation
Depending on the anatomical location and physiological context, tissue macrophages may display both pro- and anti-inflammatory phenotypes. Macrophages contribute to tissue remodelling, host defence in innate and adaptive immunity and are key to many disease processes. A clearer understanding of what determines the spectrum of innate, classical, alternative, and other activation phenotypes in macrophage populations are needed for selective targeting of pathogenic pathways.

2. Regulation of myeloid stress-surveillance in men and mice
The focus here is on the role of the mTOR pathway in regulating ‘alternative activation’ of macrophages in response to environmental stress (tumour development, infection, transplantation, ageing) and its contribution to the decline in innate immunity.

3. Innate immune responses to therapy induced tissue damage
Myeloid cell recruitment occurs in sites of tissue damage caused by chemo- or radiotherapy. Polarised myeloid cells promote the “wounding” of the tumour – providing continuous support for tumour re-growth and progression. This distinct myeloid stress response is particularly relevant to novel therapies targeting the microenvironment.

4. Tumour immunology in model systems and the clinic
We study the spontaneous development of kras/p53 driven pancreatic cancers and the response of the innate immune system to the early and late stages of disease development. Functional and phenotypic changes of the myeloid subsets correlate with the human innate immune system.

Profile

2009 - present: Clinical Senior Lecturer, Honorary Consultant in Medical Oncology; Barts Cancer Institute
2007 - Present: MRC Clinician Scientist Fellowship; Barts Cancer Institute
2007 - 2009: Clinical Lecture, Barts Cancer Institute
2009: GMC Specialist Register Medical Oncology
2008: GMC Specialist Register Haematology and Internal Medicine
2007 - 2009: Specialist Registrar in Medical Oncology, St Bartholomew’s Hospital London
2005 - 2007: Clinical Research Fellow, Translational Oncology, Barts Cancer Institute, St Bartholomew’s Hospital, London
1999 - 2005: Specialist Registrar, Centre for Internal Medicine, Department for Haematology and Oncology, University of Göttingen, Germany.

Funding

2011 –2017: Cancer Research UK Senior Cancer Research Fellowship. Mammalian target of rapamycin (mTOR) regulates innate immune function in the tumour microenvironment (£2.2 million)
2011-2013: Pancreatic Cancer Research Fund. Enhancing Oncolytic Adenovirus Efficacy in Pancreatic Cancer by Switching Tumour-Associated Macrophages (£150,000)
2009-2012: Cancer Research UK Project Grant. Cancer-Related Inflammation: Immune Tolerance and Tumour Progression Mediated Via Paracrine TNF-Alpha (£226,210)
2009-2013: MRC Case Studentship (In Collaboration with AstraZeneca). IKK2 Inhibitors in Cancer (£140,840)
2008-2011: MRC PhD studentship (£80,000)
2008-2011: Ovarian Cancer Action Project Grant. Role of MIF in Ovarian Cancer (£150,000)
2007-2011: MRC Clinician Scientist Fellowship (£896,479)

Key Publications

The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schulthesis A, Chakravarty P, Thompson RG, Kollias G, Smyth JF, Balkwill F, Hagemann T. J Clin Invest (2009) 3011-3023, PMID: 19741298

Stromal endothelin B receptor-deficinecy inhibits breast cancer growth and mestastasis. Hagemann T*, Binder C*, Sperling S, Schulz M, Pukrop T, Grimshaw MJ, Ehrenreich H.*contributed equally. Mol Cancer Ther (August 2009) 2452-2460, PMID: 19671740

Regulation of macrophage function in tumors: The multifaceted Role of NFκB. Hagemann T, Biswas SK, Lawrence T, Sica A, Lewis C. Blood (April 2009) 3139-3146. PMID: 19171876

Re-educating tumor-associated macrophages by targeting NFκB signalling. Hagemann T, Lawrence T, McNeish I, Kulbe H, Thompson RG, Charles KA, Robinson SC, Balkwill FR. J Exp Med (2008) 1261-1268. PMID: 18490490